DESCRIPTION: The objective of this research proposal is to better understand the biochemical mechanisms underlying long-term changes in neuronal function. The proposed studies will examine the biochemical underpinnings of hippocampal long-term potentiation (LTP), a widely studied cellular model for learning and memory. Specifically the investigation proposed will address the role of reactive oxygen species (ROS) as signaling molecules during LTP in area CAl of the rat hippocampal slices. The specific aims of this proposal are: 1) to test the hypothesis that ROS act as transient messengers to persistently activate protein kinase C (PKC) in hippocampal slices, 2) to test the hypothesis that ROS potentiate hippocampal synaptic transmission, and 3) to test the hypothesis that ROS potentiate hippocampal synaptic transmission via the activation of PKC. These specific aims will be addressed using direct enzymatic assays of PKC activity in hippocampal slices after incubations with various ROS-treatments. In addition, electrophysiological recordings will be performed on ROs/treated slices to assess the impact of ROS on synaptic transmission. The proposed work will provide important insights as to the functional significance of ROS as messengers that participate in processes mediating long-lasting synaptic plasticity.